Independence of first- and second-order memories in newborn rabbits.

The mammary pheromone promotes the acquisition of novel odorants (CS1) in newborn rabbits. Here, experiments pinpoint that CS1 becomes able to support neonatal learning of other odorants (CS2). We therefore evaluated whether these first- and second-order memories remained dependent after reactivation. Amnesia induced after CS2 recall selectively blocked this memory, when recall and amnesia of CS1 left the souvenir of CS2 safe; this finding partially differed from results obtained in adult mammals. Thus, in this model of neonatal appetitive odor learning, second-order memory seems to depend on first-order memory for its formation but not for its maintenance.

A pheromone to behave, a pheromone to learn: the rabbit mammary pheromone.

Birth is part of a continuum and is a major developmental change. Newborns need to adapt rapidly to the environment in terms of physiology and behaviour, and ability to locate the maternal source of milk is vital. Mechanisms have evolved resulting in the emission of olfactory cues by the mother and the processing of these cues by the young. Here, we focus on some sensory, cognitive and behavioural strategies developed by the European rabbit (Oryctolagus cuniculus) that optimize the early development of offspring. In this species, chemosensory communication between the mother and young plays a critical role in eliciting adaptive neonatal responses. In particular, lactating females release a molecule, the mammary pheromone, which has several functional impacts. It triggers orocephalic responses involved in the quick localization of nipples and sucking. Moreover, this unconditioned signal promotes rapid appetitive learning of novel odorants, acting as a potent organizer of neonatal cognition. The mammary-pheromone-induced odour memory requires consolidation/reconsolidation processes to be maintained in the long term. Finally, as this mode of conditioning also promotes learning of mixtures of odorants, it supports investigations related to the capacity of neonatal olfaction to extract biological value from the complex environment.

Pheromone-induced olfactory memory in newborn rabbits: Involvement of consolidation and reconsolidation processes.

Mammary pheromone (MP)-induced odor memory is a new model of appetitive memory functioning early in a mammal, the newborn rabbit. Some properties of this associative memory are analyzed by the use of anisomycin as an amnesic agent. Long-term memory (LTM) was impaired by anisomycin delivered immediately, but not 4 h after either acquisition or reactivation. Thus, the results suggest that this form of neonatal memory requires both consolidation and reconsolidation. By extending these notions to appetitive memory, the results reveal that consolidation and reconsolidation processes are characteristics of associative memories of positive events not only in the adult, but also in the newborn.

Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis.

The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny.

The temporal dynamics of consolidation and reconsolidation decrease during postnatal development.

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.

Memory consolidation and reconsolidation in the rat pup require protein synthesis.

Little is known about the ontogenesis of memory, whether it appears with its full characteristics or whether they emerge progressively with development. In the adult, basic characteristics of memory processing are consolidation of memory after acquisition and reconsolidation after retrieval. Here, using a conditioned aversion paradigm and postlearning or postreactivation injection of a protein synthesis inhibitor, we show that memory acquired by rat pups as early as postnatal day 3 requires time-dependent protein synthesis after both learning and reactivation. These results present the first evidence suggesting that consolidation and reconsolidation are original properties of memory function.

Abrupt emergence of long-lasting memory in the pre-weanling rat.

During the course of ontogenesis does long-lasting memory emerge progressively or abruptly, and when? To examine this question, rat pups were conditioned at different ages (3-, 10-, 12-, 15- or 18-day-old) and tested at different retention intervals: from 3 days to 1 year. Conditioned aversion memory established before 12-day-old lasts for only 1 week, but when acquired after 15 days, memory survives for more than 1 year. This defines a short temporal window of 3 days for sudden emergence of a remote memory. Our result offers a precise temporal target to explore the mechanisms involved in long maintenance of memory.

Approach memory turns to avoidance memory with age.

Ontogenetic modification of an early memory is relatively poorly understood. And an important question is whether the memory output is more determined by the age at acquisition or at retention? Here we explore the expression of odor-shock conditioning in the rat pup. Acquisition at post-natal day 6 (P6) leads to an approach response and at post-natal day 12 (P12) to an avoidance response when the retention test is 24h later. In both cases, anisomycin injected immediately post-acquisition induced a retrograde amnesia. Controls show that, in either case, short-term memory measured 4h after acquisition is not impaired and that anisomycin given after a 4h delay has no effect. Thus, at the two ages, memory involves a consolidation process. The main result is the spontaneous reversal of the conditioned response from approach acquired at P6 to avoidance when tested at P13. This phenomenon is robust as it is observed in three conditions. Moreover, amnesia induced at P6 is maintained at P13. Results are discussed in terms of maturation and/or competition of the memory traces.

Emergence of long-term memory for conditioned aversion in the rat fetus.

Pregnant rats were subjected to garlic essential oil as the conditioned stimulus and 45 min later to LiCl as the unconditioned stimulus either on embryonic Days 15 and 16 (E15 and E16) or on 18 and 19 (E18 and E19). Control dams received only garlic, LiCl, or water. Progenies were tested on garlic drinking 6 weeks after the exposure to the stimuli via the mothers. In the E18 to 19 group, rats that were exposed to paired garlic-LiCl expressed a significant aversion for garlic. In the E15 to 16 group, no significant differences appeared between subgroups. These results confirm that an associative memory can be established before birth and suggests that this ability potentially emerges in a short time window of 3 days at the end of gestation. Moreover, it appears that a long-term memory can be acquired in utero and retained to be expressed postnatally when animals are autonomous.

Muscimol diffusion after intracerebral microinjections: a reevaluation based on electrophysiological and autoradiographic quantifications.

Intracerebral muscimol injection is widely used to inactivate discrete brain structures during behavioral tasks. However, little effort has been made to quantify the extent of muscimol diffusion. The authors report here electrophysiological and autoradiographic results obtained after muscimol injection (1 microg/microl) either into the nucleus basalis magnocellularis (0.1-0.4 microl) or into the thalamic reticular nucleus (RE, 0.05-0.1 microl). In 52 rats, multiunit recordings were collected either in the RE or in the auditory thalamus during the 2 h following muscimol injection. Decreases in neuronal activity were observed up to 3 mm from the injection site; their time of occurrence was a function of the distance between the injection and recording sites. Because these decreases cannot be explained by physiological effects, they likely reflected muscimol diffusion up to the recording sites. Autoradiographic studies involved 25 rats and different experimental conditions. Optical density (OD) measures indicated that after a survival time of 15 min, a 0.05 microl injection produced a labeled area of 5.25 mm(2) at the injection site and a rostrocaudal labeling of 1.7 mm. Increasing the survival time to 60 min, or increasing the injected volume to 0.1 microl, systematically led to a larger labeled area at the injection site (8-12 mm(2)) and to a larger rostrocaudal diffusion (2.0-2.5 mm). Direct quantifications of radioactivity by a high-resolution radioimager validated the OD measures and even indicated a larger muscimol diffusion (up to 3.25 mm). Thus, these data point out that muscimol diffusion after intracerebral microinjection is larger than usually supposed. The relationships between these results and those obtained in behavioral studies are discussed.